About 40 percent of patients suffering from sepsis syndrome are infected with gram negative bacteria. This subset of patients could benefit from new anti-endotoxin therapies such as anti-lipopolysaccharide (LPS) monoclonal antibodies or LPS binding proteins. However, at $4,000 per dose, these therapies are too costly for prophylactic use. Accordingly, the plan is to develop a simple, sensitive test for early detection of gram negative bacteremia. In phase I, conserved regions of various bacterial genes were shown to be suitable targets for rapid and sensitive polymerase chain reaction (PCR) diagnosis of these lethal pathogens. To overcome limitations of this test, an LPS capture assay based on a LPS binding protein was proposed. During phase II, the plan is to compare the sensitive and highly specific PCR-based test with this LPS test.These tests will be evaluated with regard to specificity, sensitivity, and compatibility with the clinical laboratory prior to initiation of a clinical trail among patients with suspected gram negative sepsis. Introduction of these tests in clinical practice should save millions of dollars spent on the unnecessary use of new and very expensive therapies for gram negative sepsis (such as the anti-LPS monoclonal antibodies E5 and HA-1A) and improve patient selection for clinical evaluation of promising therapies such as bactericidal/permeability increasing protein (BPI).